Red blood cell transfusions are extremely common medical interventions with more than 11 million red blood cell units transfused in the United States and 75 million worldwide. Yet, it remains unclear when patients should receive red blood cell transfusions in most clinical settings. Coronary artery disease (CAD) is a common life threatening illness. Patients with acute coronary syndrome and coronary artery disease frequently become anemic because they undergo invasive procedures and are treated with multiple classes of anticoagulants. Oxygen delivery to the myocardium is flow dependent and myocardial ischemia may be precipitated by low hemoglobin concentrations. Therefore, many physicians believe that patients with underlying cardiovascular disease should be transfused to maintain hemoglobin above 10 g/dL. However, there has never been a randomized clinical trial evaluating transfusion triggers in anemic patients with active CAD. This application proposes performance of a pilot study that will be used to plan a large multicenter pragmatic trial evaluating transfusion thresholds in patients with coronary artery disease. We will perform a randomized clinical trial in 200 patients age 18 or older admitted to the hospital with 1) STEMI (ST segment elevated myocardial infarction), 2) NSTEMI (Non ST segment elevation myocardial infarction), 3) unstable angina, or 4) stable coronary artery disease patient who undergoing cardiac catherization during the index hospitalization with at least 70% obstruction by visual inspection. The patient must have a hemoglobin concentration less than 10 g/dL at the time of random allocation to liberal (10 g/dL threshold) transfusion strategy or restrictive (<8 g/dL or symptoms). Patients in the liberal transfusion strategy receive one unit of packed red cells following randomization and receive enough blood to raise the hemoglobin concentration above 10 g/dL. The Restrictive Transfusion Strategy receives transfusion if they develop symptoms of anemia or if the hemoglobin concentration falls below 8 g/dL. The aims of this study are: AIM 1: To evaluate the feasibility of conducting a research protocol that will lead to a large scale clinical trial designed to evaluate the treatment effectiveness of two transfusion threshold strategies in patients with CAD. a. To determine the eligibility and enrollment rate into this trial of transfusion triggers in CAD. b. To assess the patient characteristics of patients enrolled in this trial. c. To determine adherence rates for the transfusion protocol and test methods to minimize protocol violations. d. To determine frequencies of proposed outcomes in anemic CAD patients to use for calculating sample size for large definitive trial. AIM 2: To compare the physiologic and clinical outcome measures associated with a liberal transfusion strategy compared with a restrictive transfusion strategy to transfuse only when symptoms of anemia develop. a. To compare the mean hemoglobin concentration and number of units of red blood cells transfused between patients randomly assigned to the liberal transfusion strategy compared with the restrictive transfusion strategy. b. To determine if a liberal transfusion strategy is associated with lower incidence of composite outcome of all cause mortality at 30 days, recurrent myocardial infarction, emergent percutaneous intervention (angioplasty or stent insertion) or coronary artery bypass graft surgery within 30 days of enrollment compared to a restrictive transfusion strategy. PUBLIC HEALTH RELEVANCE: Red blood cell transfusions are extremely common medical interventions, yet, it remains unclear when patients should be transfused. This proposal will evaluate the feasibility of conducting a research protocol that will lead to a large scale clinical trial designed to evaluate the treatment effectiveness of two transfusion threshold strategies in patients with coronary artery disease.